title: Dendritic cells regulate high-speed interstitial T cell migration in the lymph node via LFA-1/ICAM-1.
abstract: T lymphocytes vigorously migrate within the paracortex of lymph nodes (LNs) in search of cognate Ags that are presented by dendritic cells (DCs). However, the mechanisms that support T cells to exert the highest motility in a densely packed LN microenvironment are not fully understood. Two-photon microscopy using LN tissue slices revealed that LFA-1 and ICAM-1 were required for high-velocity migration (>10 μm/min) with relatively straight movement. Importantly, ICAM-1 expressed by myeloid lineages, most likely DCs, but not stromal cells or lymphocytes, was sufficient to support the high-velocity migration. Visualizing DCs in the LN from CD11c-EYFP mice showed that T cells traveled over thin dendrites and the body of DCs. Interestingly, DCs supported T cell motility in vitro in chemokine- and ICAM-1-dependent manners. Moreover, an acute lymphopenic environment in the LN significantly increased LFA-1 dependency for T cell migration, indicating that lymphocyte density modulates the use of LFA-1. Therefore, our results indicate that LFA-1/ICAM-1-dependent interactions between T cells and DCs play a crucial role not only in supporting firm arrest during Ag recognition but also in facilitating the Ag scanning processes.
authors.affiliation: Department of Molecular Genetics, Institute of Biomedical Science, Kansai Medical University, Core Research for Evolutionary Science and Technology, Japan Science and Technology Agency, Hirakata, Osaka 573-1010, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Katakai
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Habiro
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kinashi
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D039521:CD11c Antigen / Q000235:genetics; D018821:CD18 Antigens / Q000235:genetics; D002465:Cell Movement / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008231:Lymphopenia; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D039521:CD11c Antigen; D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1